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Updated: May 19, 2026
08:39
Purification of Endogenous Drosophila Transient Receptor Potential Channels
Published on: December 28, 2021
Drosophila TRPML is required for TORC1 activation
Ching-On Wong1, Ruoxia Li, Craig Montell
1Department of Integrative Biology and Pharmacology, University of Texas School of Medicine, Houston, TX 77030, USA.
Current Biology : CB
|August 7, 2012
Summary
Loss-of-function mutations in TRPML1 cause mucolipidosis type IV (MLIV). In flies, TRPML1 is crucial for autophagy and lysosomal fusion; a high-protein diet rescues MLIV-like defects by modulating TORC1 signaling.
Area of Science:
- Cell Biology
- Genetics
- Physiology
Background:
- Loss-of-function mutations in TRPML1 (transient receptor potential mucolipin 1) are the cause of mucolipidosis type IV (MLIV), a lysosomal storage disorder.
- TRPML1 plays a critical role in lysosomal function and calcium signaling within cells.
Purpose of the Study:
- To investigate the function of the TRPML1 homolog in Drosophila melanogaster.
- To elucidate the relationship between TRPML1, autophagy, and TORC1 signaling.
- To explore potential therapeutic strategies for MLIV.
Main Methods:
- Generated Drosophila melanogaster mutants lacking the TRPML1 homolog.
- Assessed autophagy, lysosomal fusion, vesicle volume, and luminal Ca(2+) levels.
- Analyzed TORC1 signaling pathway activity.
- Investigated the effects of genetic TORC1 activation and dietary interventions (high-protein diet, rapamycin).
Main Results:
- Flies lacking TRPML1 exhibited incomplete autophagy, reduced pupal viability, and impaired amphisome-lysosome fusion.
- Mutant cells showed enlarged vesicles with higher luminal Ca(2+), decreased TORC1 signaling, and upregulated autophagy induction.
- Genetic activation of TORC1 or a high-protein diet rescued these defects, including pupal lethality and vesicle abnormalities.
- TORC1 activity reciprocally controlled TRPML1 function, with a high-protein diet promoting TRPML1 cortical localization, an effect blocked by rapamycin.
Conclusions:
- TRPML1 is essential for proper autophagy and lysosomal function, interacting with the TORC1 pathway.
- Modulating TORC1 signaling, potentially through dietary interventions like a high-protein diet, may offer a therapeutic approach to mitigate MLIV severity.
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